Vincendeau Lab

We develop new tools to study the functional role of HERVs during stem cell differentiation into neural cells. We directly manipulate specific HERV groups, using CRISPR technologies, in human stem cells followed by directed differentiation into neural subtypes and generation of brain organoids. In combination with large-scale gene expression analysis we elucidate the functional role and downstream effects of specific HERV groups on neural differentiation.

The tight regulation of human endogenous retroviruses (HERVs) is essential for a healthy brain and dysregulation has been associated with neurodegenerative diseases. We are combining the differentiation of stem cells into different human brain cell types with CRISPR activation as well as CRISPR inhibition of specific HERV groups to systematically dissect how dysregulation of HERVs contributes to the development of neuropathology.

Several recent studies suggest that tight regulation of human endogenous retroviruses (HERVs) is essential during developmental processes, e.g. embryonal development, where activation of HERVs leads to regulation of tissue-specific genes. In human brain development, we could show that the exact timing of HERV-K(HML-2) expression is essential for proper cortical brain patterning as well as cortical neurogenesis. We use CRISPR-based approaches in combination with stem cell differetiations, to further understand the precise regulation of HERVs in different brain cell types.

Activation of human endogenous retroviruses (HERVs) can contribute to disease, including neurodegenrative diseases, through expression of HERV-derived viral proteins or dysregulation of cellular genes. Therefore, we are investigating the effects of various environmental factors (such as exogenous viruses) on HERV activation through transcriptional profiling to understand their impact on reactivation of HERVs and contribution to disease development.